Hepatic inflammation, ballooning, and pyknosis caused by LED light exposure in a mouse model, with differential effects by age and gender.

Light-emitting diode (LED) is commonly used in lighting and digital devices in modern life, which delivers higher levels of blue light than other light sources. Previous work indicated that exposure to blue lights increases serum oxidative stress and affects hepatic functions in animals. However, the detailed hepatic pathogenesis caused by blue lights remains largely elusive. This study investigated the characteristics of hepatic injuries caused by LED light exposure in a mouse model. C57BL/6 mice were exposed the LED lights at 1000 lux, 12 h per day for 45 days or at 4500 lux, 1 h per day for 7 days. The mice were aged 8 weeks or 36 weeks in both genders and maintained under a 12 h light/dark cycle without alteration of diet pattern. Liver tissue sections were obtained for hematoxylin and eosin (H&E) and immunohistochemical staining. The mice with 1000 lux exposure displayed severe liver injuries, including inflammation, ballooning, and pyknosis, which were found to a lesser extent in the 4500 lux mice, and aging aggravated the hepatic injuries. The hepatocellular ballooning was found more severe in the males than the females. In contrast, the females expressed the F4/80 and TNF-α inflammatory markers more evidently. Taken together, LED light exposure may have detrimental effects on liver health, particularly in vulnerable groups such as the elderly and the females with excessive exposure to LED lights, even if they maintain a normal diet and regular light/dark cycles. The potential risk should be considered by both the clinicians and the public.

Novel FRET-based Immunological Synapse Biosensor for the Prediction of Chimeric Antigen Receptor-T Cell Function.

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. CARs are activated at the immunological synapse (IS) when their single-chain variable fragment (scFv) domain engages with an antigen, allowing them to directly eliminate cancer cells. Here, an innovative IS biosensor based on fluorescence resonance energy transfer (FRET) for the real-time assessment of CAR-IS architecture and signaling competence is presented. Using this biosensor, scFv variants for mesothelin-targeting CARs and identified as a novel scFv with enhanced CAR-T cell functionality despite its lower affinity than the original screened. The original CAR promoted internalization and trogocytosis, disrupting stable IS formation and impairing functionality are further observed. These findings emphasize the importance of enhancing IS quality rather than maximizing scFv affinity for superior CAR-T cell responses. Therefore, the FRET-based IS biosensor is a powerful tool for predicting CAR-T cell function, enabling the efficient engineering of next-generation CARs with enhanced antitumor potency.

Defining the Treatment Window: Early Versus Late Pulsed Dye Laser Therapy for Posttraumatic and Surgical Scars in Asian Patients.

OBJECTIVES: This retrospective study evaluates the effectiveness of pulsed dye laser (PDL) treatment in early versus late treatment groups for traumatic or postoperative scars. The study aims to determine the threshold between early and late treatment. Additionally, it investigates factors that may influence wound healing outcomes. METHODS: The medical records of 147 patients who underwent PDL treatment at our institution between January 2018 and December 2022 were retrospectively reviewed. Inclusion criteria were patients receiving PDL treatment for traumatic or postoperative scars. Out of these patients, we selected those who were willing to receive telephone interviews or re-visit at a scheduled time. Eventually, 52 participants were included in our study. A standardized questionnaire was administered to all participants during telephone interviews, encompassing inquiries regarding their medical history, treatment experiences, and the patient component of the Patient and Observer Scar Assessment Scale. Among the enrolled patients, 38 were contacted and interviewed via telephone, while the remaining 14 patients attended follow-up visits where photographs of their current skin condition were captured. The pretreatment and latest follow-up photographs obtained from the clinical database were independently scored in a blinded manner by two dermatologist reviewers using both the Vancouver Scar Scale and the Manchester Scar Scale. RESULTS: Among the 52 patients, 43 (82.7%) were successfully treated with good response. The correlation coefficients between week-to-treatment initiation and posttreatment MSS and VSS among patients with good response were 0.50 (p < 0.001) and 0.46 (p = 0.002), respectively. Given these findings, we established a treatment initiation threshold of 10 weeks, distinguishing patients into early and late treatment groups. The early treatment group showed borderline significantly lower posttreatment MSS and VSS scores than the late treatment group (MSS: 7.5 ± 2.1 vs. 9.3 ± 2.5, p = 0.011; VSS: 2.8 ± 2.0 vs. 4.5 ± 2.3, p = 0.011). Furthermore, both MSS and VSS of posttreatment showed significantly greater improvement in the early treatment group (4.4 ± 1.6 vs. 3.2 ± 1.9; p = 0.03 and 3.8 ± 1.8 vs. 2.8 ± 1.4; p = 0.04). CONCLUSIONS: Early intervention using a PDL within 10 weeks post-injury achieved better outcomes in treating traumatic and postoperative scars based on both clinical and patient opinions.

Anatomical Posterior Acetabular Plate Versus Conventional Reconstruction Plates for Acetabular Posterior Wall Fractures: A Comparative Study.

Background: Functional recovery following the surgical fixation of acetabular posterior wall fractures remains a challenge. This study compares outcomes of posterior wall fracture reconstruction using an anatomical posterior acetabular plate (APAP) versus conventional reconstruction plates. Methods: Forty patients with acetabular fractures involving the posterior wall or column underwent surgery, with 20 treated using APAPs (APAP group) and 20 with conventional pelvic reconstruction plates (control group). Baseline patient characteristics, intraoperative blood loss and time, reduction quality, postoperative function, and postoperative complications were compared using appropriate non-parametric statistical tests. A general linear model for repeated measures analysis of variance was employed to analyze trends in functional recovery. Results: No significant differences were observed in baseline characteristics. APAP significantly reduced surgical time by 40 min (186.5 ± 51.0 versus 225.0 ± 47.7, p =0.004) and blood loss (695 ± 393 versus 930 ± 609, p = 0.049) compared to conventional plates. At 3 and 6 months following surgery, the APAP group exhibited higher functional scores (modified Merle d'Aubigné scores 10 ± 1.8 versus 7.8 ± 1.4, p < 0.001; 13.4 ± 2.8 versus 10.1 ± 2.1, p = 0.001), converging with the control group by 12 months (modified Merle d'Aubigné scores 14.2 ± 2.6 versus 12.7 ± 2.6, p = 0.072; OHS 31.6 ± 12.3 versus 30.3 ± 10.1, p = 0.398). Radiologically, the APAP group demonstrated superior outcomes (p = 0.047). Complication and conversion rates to hip arthroplasty did not significantly differ between groups (10% versus 15%, p = 0.633). Conclusions: The use of an APAP in reconstructing the posterior acetabulum significantly reduces surgical time, decreases intraoperative blood loss, and leads to earlier functional recovery compared to conventional reconstruction plates. The APAP provides stable fixation of the posterior wall and ensures the durable maintenance of reduction, ultimately yielding favorable surgical outcomes.

Construction and validation of a synthetic phage-displayed nanobody library.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Incubation of Amyloidogenic Peptides in Reverse Micelles Allow Active Control of Oligomer Size and Study of Protein-Protein Interactions.

Studies of the structure and dynamics of oligomeric aggregates of amyloidogenic peptides pose challenges due to their transient nature. This concept article provides a brief overview of various nucleation mechanisms with reference to the classical nucleation theory and illustrates the advantages of incubating amyloidogenic peptides in reverse micelles (RMs). The use of RMs not only facilitates size regulation of oligomeric aggregates but also provides an avenue to explore protein-protein interactions among the oligomeric aggregates of various amyloidogenic peptides. Additionally, we envision the feasibility of preparing brain tissue-derived oligomeric aggregates using RMs, potentially advancing the development of monoclonal antibodies with enhanced potency against these pathological species in vivo.

Streptococcus thermophilus iHA318 Improves Dry Eye Symptoms by Mitigating Ocular Surface Damage in a Mouse Model.

Dry eye is a complicated ocular surface disease that causes discomfort, visual disturbance, and frequently observed ocular surface damage. Emerging hypotheses suggest probiotics may help relieve dry eye symptoms by modulating inflammation and oxidative stress. This study aimed to investigate the therapeutic effects of Streptococcus thermophilus iHA318 probiotics on dry eye using in vitro assays and an in vivo murine model of ultraviolet B (UVB) radiation-induced dry eye. In vitro analyses revealed that S. thermophilus iHA318® exhibited antioxidant activity and anti-inflammatory effects by inhibiting reactive oxygen species production and suppressing inflammatory cytokines. For the in vivo study, female ICR mice were assigned to normal control, UVB-induced dry eye, and UVB+iHA318 treatment groups. UVB exposure significantly decreased tear volume and tear film breakup time (TBUT) compared to normal controls. Supplementation with S. thermophilus iHA318® via oral gavage markedly improved tear production and TBUT on day 7 post-UVB exposure. Ocular surface photography demonstrated improved gradings of corneal opacity, smoothness, and lissamine green staining in the iHA318 group versus the UVB group. Topographical analysis further revealed improvement in the UVB-induced corneal irregularities by iHA318 treatment. Collectively, these results indicate that S. thermophilus iHA318 exerts a protective effect against dry eye symptoms by mitigating oxidative stress and inflammation, thereby preserving tear film stability and ocular surface integrity. This probiotic strain represents a promising therapeutic approach for managing dry eye syndrome.

The Characteristics and Two-Year Neurodevelopmental Outcomes of Home Oxygen Therapy among Preterm Infants with Bronchopulmonary Dysplasia: A Retrospective Study in a Medical Center in Taiwan.

Home oxygen therapy (HOT) is frequently used as a therapeutic strategy for children experiencing chronic oxygen dependency associated with bronchopulmonary dysplasia (BPD). Recent studies have highlighted substantial variations in the characteristics and outcomes of infants requiring oxygen, primarily due to the absence of a consensus on the management of HOT in infants with BPD. We conducted this retrospective study and reviewed the medical records of extremely and very preterm infants who were diagnosed with BPD in a tertiary center in northern Taiwan from January 2020 to September 2021. Their neurodevelopmental outcomes were evaluated at 18 to 24 months of corrected age. A total of 134 patients diagnosed with BPD were divided into a HOT group (n = 39) and a room air group (n = 95). The children in the HOT group had a higher incidence of hemodynamic significant patent ductus arteriosus (PDA) (p = 0.005) and PDA ligation (p = 0.004), high-frequency oscillatory ventilation (p < 0.001), nitrogen oxide inhalation (p < 0.001), pulmonary hypertension (p = 0.01), and longer invasive ventilation (p < 0.001), as well as longer hospitalization (p < 0.001). A multivariate logistic regression model demonstrated that prolonged invasive ventilation (OR = 1.032, 95% CI 0.984-1.020, p = 0.001) was correlated with oxygen dependency in children. Infants with BPD born at advanced gestational age (OR = 0.760, 95%CI 0.582-0.992, p = 0.044) had a decreasing risk of requiring HOT. The children in the HOT group had a higher incidence of emergency room visits (p < 0.001) and re-hospitalization (p = 0.007) within one year of corrected age. The neurodevelopmental outcomes revealed the HOT group had an increasing portion of moderate to severe cognitive delay (18.2% vs. 3.7%, p = 0.009) and moderate to severe language delay (24.2% vs. 6.1%, p = 0.006) at 18 to 24 months of corrected age. In conclusion, infants with BPD necessitating HOT required prolonged invasive ventilation during hospitalization and exhibited a greater prevalence of unfavorable neurodevelopmental outcomes at 18 to 24 months of corrected age as well.

Bacteria Contaminants Detected by Organic Inverter-Based Biosensors.

The importance of bacteria detection lies in its role in enabling early intervention, disease prevention, environmental protection, and effective treatment strategies. Advancements in technology continually enhance the speed, accuracy, and sensitivity of detection methods, aiding in addressing these critical issues. This study first reports the fabrication of an inverter constructed using crosslinked-poly(4-vinylphenol) (C-PVP) as the dielectric layer and an organic complementary metal-oxide semiconductor (O-CMOS) based on pentacene and N,N'-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (PTCDI-C13) as a diagnostic biosensor to rapidly detect bacterial concentration. Bacteria including Escherichia coli O157, Staphylococcus aureus ATCC25922, and Enterococcus faecalis SH-1051210 were analysed on the inverters at an ultra-low operating voltage of 2 V. The high density of negative charge on bacteria surfaces strongly modulates the accumulated negative carriers within the inverter channel, resulting in a shift of the switching voltage. The inverter-based bacteria sensor exhibits a linear-like response to bacteria concentrations ranging from 102 to 108 CFU/mL, with a sensitivity above 60%. Compared to other bacterial detectors, the advantage of using an inverter lies in its ability to directly read the switching voltage without requiring an external computing device. This facilitates rapid and accurate bacterial concentration measurement, offering significant ease of use and potential for mass production.

Safety and oncological outcome of early intraoperative intravesicle mitomycin C vs. deferred instillation in patients receiving robot-assisted radical nephroureterectomy.

Introduction: Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE. Methods: This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes. Results: A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group. Conclusion: IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department.

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Current updates for hyperuricemia and gout in age-related macular degeneration.

The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro-inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age-related macular degeneration (AMD), a sight-threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro-oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal-induced and non-crystal-induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations.

The Removal of Strontium Ions from an Aqueous Solution Using Na-A Zeolites Synthesized from Kaolin.

Sr2+ ions in an aqueous solution were removed using Na-A zeolites synthesized from kaolin, a natural mineral. Na-A zeolites with high crystallinity were synthesized using NaOH/kaolin mass ratios of 0.6 (ZK06) and 0.9 (ZK09). The adsorption reached equilibrium within 120 min. The adsorption data obtained from experiments for Sr2+ using ZK06 and ZK09 were appropriately analyzed with pseudo-second-order kinetic and Langmuir isotherm models. Comparing the maximum adsorption capacities (qm) of ZK06 and ZK09 for Sr2+, the highest values were obtained at 1.90 and 2.42 mmol/g, respectively. Consequently, the Na-A zeolites synthesized from kaolin can be evaluated as adsorbents with high adsorption capacities for the removal of Sr2+, proportional to the degree of their crystallinity.

Anti-SARS-CoV-2 Nucleocapsid Antibody Positivity Three Years after COVID-19.

The accurate identification of individuals without prior infection with severe acute respiratory syndrome coronavirus 2 is pivotal for seroepidemiological studies and vaccine trials. Owing to widespread vaccination against coronavirus disease 2019 (COVID-19), the anti-nucleocapsid antibody continues to serve as a valuable marker for individuals without a history of COVID-19. This study aimed to comprehensively assess anti-nucleocapsid antibody positivity using diverse commercial and in-house immunoassays among individuals who contracted COVID-19 more than three years earlier. We enrolled 44 participants with laboratory-confirmed COVID-19 between January and May 2020 from the Seoul National University Hospital and its community treatment centers. The results showed anti-nucleocapsid antibody positivity ranging from 45.5% to 87.9%, depending on the immunoassay. This study highlights the importance of considering the limited anti-nucleocapsid antibody positivity in individuals, with a history of distant COVID-19, in seroepidemiological or vaccine research.

Musculoskeletal Pain, Physical Activity, Muscle Mass, and Mortality in Older Adults: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA).

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in older adults, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyses were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived over a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pains. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pains. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

Urgent Management of Penetrating Ocular Injury: A Case Report and Review of the Literature.

Ocular globe injury is a severe ophthalmic emergency that requires immediate attention in the emergency department. In this case report, we present a 35-year-old male who suffered a penetrating ocular injury and globe rupture caused by a nail puncture. The patient presented with severe pain and visual loss and was treated with tetanus vaccination, empirical antibiotics, and pain control, followed by an urgent orbital computed tomography (CT) scan and consultation with an ophthalmologist. The CT scan revealed a retained nail in the ocular space, and an urgent operation was performed to repair the eyeball rupture, remove the intraocular foreign body, and perform an anterior vitrectomy. The patient was discharged 6 days after the operation with a visual acuity of 20/400 and an ocular trauma score of 34. This case highlights the importance of initial emergency physician decision-making and the need for a thorough history-taking and examination when encountering penetrating ocular injuries.

Corrigendum to "Development and Asian-wide validation of the Grade for Interpretable Field Triage (GIFT) for predicting mortality in pre-hospital patients using the Pan-Asian Trauma Outcomes Study (PATOS)" [The Lancet Regional Health - Western Pacific 34 (2023) 100733].

[This corrects the article DOI: 10.1016/j.lanwpc.2023.100733.].